Nadir paranazal sinüs kanserlerinde yeni tanımlanan reseptör tirozin kinaz mutasyonları ve potansiyel fonksiyonel etkileri

Bakiye Goker Bagca; Sercan Göde; Göksel Turhal; Neslihan Pınar Özateş; Ali Veral; Cumhur Gündüz; Çığır Avcı

doi:10.19161/etd.1262612

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Nadir paranazal sinüs kanserlerinde yeni tanımlanan reseptör tirozin kinaz mutasyonları ve potansiyel fonksiyonel etkileri

Öz

Amaç: Paranazal sinüs kanserleri oldukça nadir ve heterojen bir hastalık grubudur. Maksiler sinüs skuamoz hücreli karsinomu, paranazal sinüs kanserlerinin anatomik ve histolojik olarak en yaygın alt tipidir. Bu kanserin genetik profiline dair bilginin sınırlı olması, hastaların hedefli tedavi seçeneklerinden yararlanamamasına neden olmaktadır. Çalışmamızda bu nadir kanserdeki reseptör tirozin kinaz mutasyonlarının tanımlanması ve mutasyonların olası fonksiyonel etkilerinin tahmin edilmesi amaçlanmıştır. Gereç ve Yöntem: Bu amaçla 30 olgunun tümörüne ait FFPE dokulardan DNA izolasyonu gerçekleştirildi, olguların mutasyon profili yeni nesil sekanslama yöntemi ve biyoinformatik değerlendirme ile belirlendi. Belirlenen patojenik/ olası patojenik varyantların fonksiyonel etkileri farklı in silico araçlar yardımıyla tahminlendi. Bulgular: Olgularının tamamında en az bir adet patojenik/olası patojenik KIT, PDFGRA ve RET mutasyonu tanımlandı. KIT geninin katalitik bölgesindeki mutasyonların kinaz aktivitesini arttıracağı tahmin edildi ve bu mekanizmanın paranazal sinüs kanserlerinde sürücü rol oynayabileceği ve yeni bir tedavi hedefi oluşturabileceği önerildi. PDFGRA genindeki p.P567P ve p.D1074D mutasyonlarının tümörün erken tanısında kullanılabilecek potansiyel biyobelitrteçler olabileceği önerildi. Sonuç: Reseptör tirozin kinaz mutasyonlarının paranazasl sinüs kanserlerinde de önemli rol oynayabileceğinin belirlenmiş olması özellikle artmış kinaz aktivitesini hedefleyen tedavi yaklaşımlarını bu olguların erişimine sunma potansiyeli taşıması bakımından oldukça önemlidir.

Anahtar Kelimeler

Novel receptor tyrosine kinase mutations in rare paranasal sinus cancers and their potential functional implications

Abstract

Objective: Paranasal sinus cancers are a very rare and heterogeneous group of diseases. Maxillary sinus squamous cell carcinoma is the most common anatomical and histological subtype of paranasal sinus cancers. The limited knowledge about the genetic profile of this cancer causes patients not to benefit from targeted therapy options. In our study, we aimed to identify receptor tyrosine kinase mutations in this rare cancer and to predict the possible functional effects of these mutations. Materials and Methods: For this purpose, DNA isolation was performed from FFPE tissues belonging to the tumors of 30 cases, and the mutation profile of the cases was determined by next generation sequencing and bioinformatics analyses. The functional effects of the determined pathogenic/likely pathogenic variants were estimated by using different in silico tools. Results: At least one pathogenic/likely pathogenic KIT, PDFGRA and RET mutations were identified in all cases. It was predicted that mutations in the catalytic region of the KIT gene would increase kinase activity, and it was suggested that this mechanism could play a driver role in paranasal sinus cancers and create a new therapy target. It has been suggested that the p.P567P and p.D1074D mutations in the PDFGRA gene may be the potential biomarkers that can be used in the early diagnosis of the tumor. Conclusion: The determination that receptor tyrosine kinase mutations may play an important role in paranasal sinus cancers is crucial in terms of the potential to offer treatment approaches targeting increased kinase activity to these patients.

Keywords

Supporting Institution

Ege Üniversitesi BAP Koordinatörlüğü

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Details

Primary Language

Turkish

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Bakiye Goker Bagca ^*
0000-0002-5714-7455
Türkiye

Sercan Göde
0000-0002-2148-0723
Türkiye

Göksel Turhal
0000-0003-0020-1921
Türkiye

Neslihan Pınar Özateş
0000-0001-6856-4644
Türkiye

Ali Veral
0000-0003-0343-9978
Türkiye

Cumhur Gündüz
0000-0002-6593-3237
Türkiye

Çığır Avcı
0000-0001-8251-4520
Türkiye

Publication Date

March 15, 2023

Submission Date

June 27, 2022

Acceptance Date

October 17, 2022

Published in Issue

Year 2023 Volume: 62 Number: 1

DOI

https://doi.org/10.19161/etd.1262612

IZ

https://izlik.org/JA57KL75DG

Cite

RIS / Bibtex

Vancouver

1.Bakiye Goker Bagca, Sercan Göde, Göksel Turhal, Neslihan Pınar Özateş, Ali Veral, Cumhur Gündüz, Çığır Avcı. Nadir paranazal sinüs kanserlerinde yeni tanımlanan reseptör tirozin kinaz mutasyonları ve potansiyel fonksiyonel etkileri. EJM. 2023 Mar. 1;62(1):139-54. doi:10.19161/etd.1262612